Effects of Fe2+ addition to sugarcane molasses on poly-γ-glutamic acid production in Bacillus licheniformis CGMCC NO. 23967.

BACKGROUND: Poly-γ-glutamic acid (γ-PGA) is biodegradable, water-soluble, environment-friendly, and edible. Consequently, it has a variety of industrial applications. It is crucial to control production cost and increase output for industrial production γ-PGA. RESULTS: Here γ-PGA production from sugarcane molasses by Bacillus licheniformis CGMCC NO. 23967 was studied in shake-flasks and bioreactors, the results indicate that the yield of γ-PGA could reach 40.668 g/L in a 5L stirred tank fermenter. Further study found that γ-PGA production reached 70.436 g/L, γ-PGA production and cell growth increased by 73.20% and 55.44%, respectively, after FeSO4·7H2O was added. Therefore, we investigated the metabolomic and transcriptomic changes following FeSO4·7H2O addition. This addition resulted in increased abundance of intracellular metabolites, including amino acids, organic acids, and key TCA cycle intermediates, as well as upregulation of the glycolysis pathway and TCA cycle. CONCLUSIONS: These results compare favorably with those obtained from glucose and other forms of biomass feedstock, confirming that sugarcane molasses can be used as an economical substrate without any pretreatment. The addition of FeSO4·7H2O to sugarcane molasses may increase the efficiency of γ-PGA production in intracellular.

Prognostic Significance and Diagnostic Value of Overexpressed lncRNA PVT1 in Colorectal Cancer.

BACKGROUND: The aim of this study is to investigate the expression of lncRNA PVT1 in CRC tissue compared to adjacent normal tissues, and reveal the association between lncRNA PVT1 expression level and the clinicopathological characteristics of patients with CRC. METHODS: We detected the lncRNA PVT1 relative expression of cancerous tissues in 130 patients with CRC by using real-time quantitative polymerase chain reaction. At the same time, we collected the clinicopathological and prognostic information. RESULTS: IncRNA PVT1 was overexpressed in CRC tissues compared to paired-adjacent normal tissues and the high expression rate was 72.31%. High expression of lncRNA PVT1 predicts a later tumor stage (p = 0.001), poorer tissue differentiation (p = 0.019), and higher plasma CEA level (p = 0.043). Additionally, the lncRNA PVT1 expression was closely related to lymph node metastasis (N1/N2 vs. N0) and distant metastasis (M1 vs. M0) in CRC patients (p = 0.002; p = 0.003), but not to tumor T classification (p = 0.314). The result of prognostic analysis indicated that the 1-year and 3-year DFS of the lncRNA PVT1 low and high expression patients were 93.8% and 81.1%, 69.3% and 44.7%, respectively. The median DFS was 44 months in low expression group and 26 months in high expression group, with statistical significance (p = 0.021). COX multivariate analysis showed that TNM staging (III/IV vs. I/II: HR = 6.342, 95% CI: 2.994 - 13.433, p < 0.001) and the lncRNA PVT1 expression (high expression vs. low expression: HR = 3.744, 95% CI: 1.493 - 9.392, p = 0.005) was closely related to DFS in CRC patients. As with tumor TNM staging, lncRNA PVT1 expression was also an independent prognostic predictor of DFS. The proportion of lncRNA PVT1 high expression (fold change ≥ 1.725) was higher than that of elevated CEA ( > 5 ng/mL) in different CRC stages, especially, there was a significant difference in stage I patients (X2 = 41.717, p < 0.0001). CONCLUSIONS: The lncRNA PVT1 was over-expressed in CRC tissues, which indicated a poor prognosis. The lncRNA PVT1 expression is far higher than the plasma CEA level in the early stage patients, which has the potential diagnostic value for early stage CRC.

LncRNA PVT1: a Novel Therapeutic Target for Cancers.

BACKGROUND: Long non-coding RNA PVT1, as an important carcinogenic lncRNA, is highly expressed in many malignant tumors and suggests a poorer prognosis. It can promote the occurrence and development of cancers by affecting cell proliferation, migration, invasion and apoptosis. This article reviews the progress of lncRNA PVT1 on cancer therapy, in order to facilitate the in-depth study of lncRNA PVT1 acting as a promising target for therapy in cancers. METHODS: We extracted all relevant studies of lncRNA PVT1 on the treatment of cancers by searching electronic databases Pubmed, Embase, Web of Science from inception to November 30, 2017. RESULTS: Accumulating vigorous evidence has shown that lncRNA PVT1 performs a significant carcinogenic activity in various cancers, for instance, negatively modulating miRNA as a ceRNA or a molecular sponge to exert tumor-promoting effect. Based on the critical role of lncRNA PVT1 in the pathogenesis of cancers, numerous studies have already demonstrated that lncRNA PVT1 might serve as a potential therapeutic target for various cancers, such as non-small cell lung cancer, hepatocellular carcinoma, gastric cancer, breast cancer, glioma, etc. CONCLUSIONS: Numerous studies have indicated that lncRNA PVT1 will most likely become a novel target for cancer therapy with the deepening systematic research.

Evaluation of the clinical application of multiple tumor marker protein chip in the diagnostic of lung cancer.

BACKGROUND: The early diagnostic of lung cancer plays an important role in the prognosis of surgical treatment among lung cancer patients. To evaluate the clinical application of multi-tumor markers protein biochip in the diagnosis of lung cancer, 12 tumor markers were detected in patients with different stages of lung cancer. METHODS: Serum CA125, CA19-9, Ferritin, CA15-3, CA242, CEA, AFP, NSE, PSA, f-PSA, HGH, and ß-HGH were assessed in 506 patients, with 224 patients with lung cancer (including 123 cases of adenocarcinoma, 30 squamous cell carcinoma, 54 small-cell carcinoma, and 17 non classification), 159 patients with benign lung disease and 90 healthy people control by the C-12 multiple tumor protein-chip detective system. RESULTS: The positive rate of C-12 (77.23%) in lung cancer was significantly higher than that of benign lung disease (13.84%) and healthy people (9.76%) (P < .01). In lung cancer, the positive rate of CA199, NSE, CEA, CA242, Ferritin, f-PSA, and CA125 were significantly higher than that of benign lung disease and healthy people. In adenocarcinoma, the positive rate of CA125 (73.53%) was significantly higher than that of squamous cell carcinoma (36.67%) and small-cell carcinoma (56.62%). CONCLUSION: The C-12 multiple tumor protein-chip detective system has acceptable sensitivity in the diagnostic of lung cancer.

Long Noncoding RNA PVT1 as a Potent Predictor of Prognosis in Cancers: a Meta-Analysis.

BACKGROUND: Plasmacytoma variant translocation 1 (PVT1), an oncogenic long noncoding RNA located in a recognized cancer-risk gene region-8q24, is significantly overexpressed in various cancers. Many studies have found that high expression of PVT1 was correlated with poor prognosis. METHODS: This meta-analysis was performed by searching electronic databases Pubmed, Web of Science, Chinese National Knowledge Infrastructure, WanFang, and ChongQing VIP for eligible papers on the prognostic impact and clinicopathological characteristics of PVT1 expression in cancer from inception to January 31, 2017. The hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were computed to estimate the pooled effect of PVT1 on prognosis of cancers using Stata 12.0 version software. RESULTS: Thirteen studies were finally included in this review with a total of 1559 patients. The pooled result indicated that overexpressed PVT1 predicts a poorer prognosis of cancerous patients for overall survival (HR = 1.91, 95% CI: 1.61 - 2.26, p < 0.001) and disease-free survival (HR = 1.90, 95% CI: 1.46 - 2.48, p < 0.001) or recurrencefree survival (HR = 1.77, 95% CI: 1.24 - 2.52, p = 0.002) or progression-free survival (HR = 2.84, 95% CI: 1.67 - 4.82, p < 0.001). High expression of PVT1 was closely associated with tumor-node-metastasis (TNM) stage (III/IV vs. I/II: OR = 3.19, 95% CI: 2.43 - 4.18, p < 0.001), and the significant correlation between PVT1 expression and TNM stage is found in T classification (T3/4 vs. T1/2: OR = 6.48, 95% CI: 2.93 - 14.31, p < 0.001) and lymph node metastasis (present vs. absent: OR = 2.56, 95% CI:1.36 - 4.80, p = 0.003), but not in distant metastasis of patients with cancers (yes vs. no: OR = 2.50, 95% CI: 0.72 - 8.66, p = 0.15). Furthermore, the cancerous patients with high PVT1 expression had a worse histological differentiation than those with low PVT1 expression (undifferentiated/poorly vs. moderately/well: OR = 1.48, 95% CI: 1.02 - 2.14, p = 0.039). CONCLUSIONS: PVT1 could serve as a potent predicator of prognosis in different types of cancers.

Efficient production of pullulan by Aureobasidium pullulans using a multi-objective optimization strategy with orthogonal experimental design coupling artificial neural network and genetic algorithm.

Efficient pullulan production has long been a central research focus. This study used maltodextrin as the carbon source for pullulan production by Aureobasidium pullulans fermentation. A hybrid optimization approach, integrating orthogonal experimental design (OED), backpropagation artificial neural network (BP-ANN), and elite strategy non-dominated sequential genetic algorithm-II (NSGA-II), was developed. Range analysis based on OED revealed that MgSO4·7H2O significantly affects production but less impacts molecular weight, while pH notably influences molecular weight with a lesser effect on production, underscoring the need for multi-objective optimization. The BP-ANN model showed strong predictive capabilities, with goodness-of-fit values of 0.984 and 0.980 for production and molecular weight, respectively. Using this model as the fitness function for the optimization algorithm enhanced efficiency. Taking cost factors into account, the BP-ANN-NSGA-II algorithm identified the optimal fermentation medium conditions, resulting in a 6.89 % increase in production, a 368.97 % increase in molecular weight, and a 42.49 % reduction in cost. The maximum comprehensive optimization efficiency is 63.73 %, and the multi-objective optimization is better than the single objective optimization. This method significantly guides the improvement of pullulan fermentation optimization efficiency.

Novel multifunctional environmentally friendly degradable zeolitic imidazolate frameworks@poly (γ-glutamic acid) hydrogel with efficient dye adsorption function.

Recently, metal-organic frameworks (MOFs) have been widely developed due to the rich porosity, excellent framework structure and multifunctional nature. Meanwhile, a series of MOFs crystals and MOF-based composites have been emerged. However, the widespread applications of MOFs are hindered by challenges such as rigidity, fragility, solution instability, and processing difficulties. In this study, we addressed these limitations by employing an in-situ green growth approach to prepare a zeolitic imidazolate frameworks-8@poly (γ-glutamic acid) hydrogel (ZIF-8@γ-PGA) with hierarchical structures. This innovative method effectively resolves the inherent issues associated with MOFs. Furthermore, the ZIF-8@γ-PGA hydrogel is utilized for dye adsorption, demonstrating an impressive maximum adsorption capacity of 1130 ± 1 mg/g for methylene blue (MB). The adsorption behavior exhibits an excellent agreement with both the kinetic model and isotherm. Meanwhile, because the adsorbent raw materials are all green non-toxic materials, multiple applications of materials can also be realized. Significantly, the results of antibacterial experiments showed that the ZIF-8@γ-PGA hydrogel after in-situ growth of ZIF-8 had better antibacterial properties. Thus, the ZIF-8@γ-PGA hydrogel has great potential for development in wound dressings, sustained drug owing to its biocompatibility and antibacterial activity.

Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Comparative phenotype and microRNAome in developing anthers of wild-type and male-sterile Lycium barbarum L.

Lycium barbarum L. (L. barbarum) is an economically important plant, as its fruit is highly marketable for its healthy nutrient content. In this study, we characterized the anther development of a major cultivar (Ningqi No. 1) and a male-sterile mutant (Ningqi No. 5) of L. barbarum. We initially investigated the phenotypes of Ningqi No. 1 and Ningqi No. 5 using microscopy and chemical staining, which showed that Ningqi No. 5 failed in the degradation of anther callose, leading to an absence of mature pollen grains and thus to male sterility. Then, to understand the dynamic profile of miRNA expression during the development of the anthers, we collected anther samples from both Ningqi No. 1 and Ningqi No. 5 throughout anther development, and we further identified 137 novel miRNAs from these anther samples by using next-generation deep sequencing technology. Of these 137 novel miRNAs, 96 miRNAs were conserved miRNAs classified into 65 miRNA families, including a few well-known miRNA families related to anther development, such as miR156, miR159 and miR172. In addition, the remaining 41 miRNAs were considered lineage-specific miRNAs, which had no orthologues in other species. The expression data showed that 45 of the 137 miRNAs were differentially expressed in the different samples, including 4 Ningqi No. 5-specific miRNAs and 15 stage-specific miRNAs. The expression patterns of six miRNAs and their predicted targets were verified by Q-PCR, and one of miRNAs and its target were chosen for transient co-expression in Nicotiana benthamiana leaves to verify the correlations between the miRNA and its predicted target. Overall, the identification of the miRNAs in the anther development of Ningqi No. 1 and Ningqi No. 5 provides a valuable resource for understanding the molecular mechanisms of male sterility in L. barbarum.

[Screening and expression of tumor markers in colorectal carcinoma].

OBJECTIVE: To screen the tumor markers of colorectal carcinoma and to investigate their expression in preoperative and postoperative serum. METHODS: The distinct proteins in serum were detected in 87 cases of colorectal carcinoma, 68 cases of benign colorectal diseases and 56 healthy people by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The distinct proteins in serum were detected in 87 cases of colorectal carcinoma pre-operation and within 15 days post operation with the same methods. RESULTS: Two proteins with mass-to-charge ratios of 5955 Da and 5972 Da were screened. Compared with benign colorectal diseases and healthy control, the expression of the two proteins was obviously up-regulated in colorectal carcinoma (P < 0.01). Compared with pre-operation, the expression on the 1(st) day post operation was obviously up-regulated (P < 0.01), and the expression decreased to pre-operative level on the 4(th) day post operation. The expression of the two proteins turned out to be a descendent tendency form the 4(th) to 15(th) day post operation, but did not reach the normal level as found in healthy control. CONCLUSIONS: Two proteins with mass-to-charge ratios of 5955 Da and 5972 Da could be regarded as tumor markers in colorectal carcinoma, the expression may has some regularity.

Serum peptidome patterns of hepatocellular carcinoma based on magnetic bead separation and mass spectrometry analysis.

BACKGROUND/AIMS: The only hope for a cure from hepatocellular carcinoma (HCC) rests on early diagnosis. The present study aims to determine serum peptidome patterns for early diagnosis of HCC. MATERIALS AND METHODS: To identify novel peptidome patterns for diagnosing HCC, serum from31 healthy volunteers and 32 HCC patients were subjected to a comparative proteomic analysis using a ClinProt Kit combined with mass spectrometry (MS). This approach allows the determination of peptidome patterns that are able to differentiate the HCC from healthy volunteers. For further validation, the diagnostic and differential diagnostic capabilities of the peptidome patterns were verified blindly by an independent group of sera consisted of 31 HCC, 23 liver fibrosis and 33 healthy volunteers. RESULTS: A Quick Classifier Algorithm was used to construct the peptidome patterns for the identification of HCC from the control samples. One of the identified peaks at m/z 7771 was used to construct the peptidome patterns with almost 100% accuracy. Furthermore, the peptidome patterns could also differentiate the validation group with high accuracy. CONCLUSION: These results suggest that the ClinProt Kit combined with MS achieves significantly high accuracy for HCC diagnosis and differential diagnosis.

[Effects of irrigation amount on leaf structure, photosynthetic physiology, and fruit yield of Lycium barbarum in arid area].

Lycium barbarum is an important traditional medicinal plant in China. Under controlled condition, a field experiment was conducted to study the effects of different monthly irrigation quota on the leaf structure, photosynthetic physiology, and fruit yield of L. barbarum, aimed to determine an appropriate irrigation amount for the plant. When the monthly irrigation quota was less than 900 m3 x hm(-2), the leaf area, leaf thickness, palisade tissue thickness, cell tense ratio (CTR), net photosynthetic rate (Pn), intrinsic water use efficiency (WUE), stomatal limitation value (Ls), and fruit yield of L. barbarum all increased significantly with monthly irrigation quota, while leaf stoma density and intercellular CO2 concentration (Ci) showed a reverse trend. When the irrigation quota was more than 900 m3 x hm(-2), the Ci increased with irrigation quota, the leaf area, stoma density, and fruit yield had no obvious change, whereas the other indices showed a reverse trend. The leaf transpiration rate and Gs were the highest at irrigation quota 450 m3 x hm(-2), being 8.02 and 324 mmol x m(-2) x s(-1), respectively; whereas at other irrigation quota, these two indices were lower than the control. In terms of saving water, the monthly irrigation quota 900 m3 x hm(-2) was more appropriate for Lycium barbarum.

[Comparative study of recurrent colon cancer and recurrent rectal cancer after radical resection].

OBJECTIVE: To explore the difference in tumor biological behaviors and prognosis between recurrent colon cancer and recurrent rectal cancer after radical operation. METHODS: Complete clinical and follow-up data of 132 patients with colorectal cancer developed recurrence,including 36 colon cancers and 96 rectal cancers, after curative resection were retrospectively analyzed and compared with respect of clinical pathological features and prognosis between colon and rectal cancer. RESULTS: Significant differences were found in primary tumor gross type, histological type, tumor differentiation and lymph node metastasis between colon and rectal cancer(P<0.05). Colon cancer recurred earlier than rectal cancer after radical surgery with the median time to recurrence being 14.0 months and 21.5 months, respectively(P=0.028). The difference in multiple sites recurrence was also found between colon(n=16, 44.4%) and rectal cancer(n=65, 67.7%)(P=0.014). The 3-year survival rate of recurrent rectal cancer was better than that of colon cancer (24.8% vs 15.6%, P=0.026). CONCLUSION: There are some differences in tumor biological behaviors between colon and rectal cancer, and the prognosis of rectal cancer with recurrence is better than that of colon cancer.